JP2015507191A5 - - Google Patents

Description

As shown, the plurality of grooves and channels 30 extend substantially radially from the fluid passageway 34 and direct the fluid radially inward and outward depending on the location of the flow distributor 24. The height or depth of the groove tapers from the center / feed port (eg, fluid passage 34 ) to a lower height in the outer peripheral region of the flow distributor 24. This taper aspect ratio is the subject of various publications that provide general design guidelines (eg, Gebauer et al., “Efficiency of Preparative and Process Column Distribution Systems,” Journal of Chromatography 1006 (2003) 45-60. See). This taper shape can help minimize pressure gradients in the radial and axial directions that can adversely affect column performance (eg, efficiency) by dispersion of target molecules traveling through the packed bed.

A fitting is a mechanical attachment that is fastened or secured to a flow distributor to send liquid to or remove liquid from the flow distributor and the tube in which it is placed. To send fluid, the fitting has a fluid feed hole formed through the fitting along the central axis of the fitting. The fitting further includes one or more features that are received in the fitting holes of the flow distributor to hold the fitting. As shown in FIGS. 1, 2 a and 2 b, in this example, the fitting 38 has a threaded end 40 (eg, a M30 × 3.5 threaded end) that engages the fitting hole 26. The fitting 38 further includes a nut portion 42 that can be gripped by a tool (for example, a torque wrench) for rotating and fixing the fitting 38 in the fitting hole 26. In some embodiments, the fitting 38 includes other types of connection mechanisms, such as adhesives, welds, plug or luer connections, or other sufficient connection techniques.

The fitting 38 may have different additional features based on its installation location. For example, the inlet fitting 38a installed in the upper flow distributor 24a may have a connection feature at the end of the fitting opposite the threaded end. A connection feature such as a hose connection allows the hose or pipe to be easily connected to the fitting. In this example, the inlet fitting 38a defines a recess 44 sized and configured to be received by a hose fitting, such as a sanitary fitting (eg, triple clamp connection or cam lock) type hose fitting.

Second, a properly sized flow distributor 24 is slightly larger than the inside diameter (“ID”) of the tube, eg, about .25%, 0.05 to about 3.0, 1.0.1.5. , 2.0.2.5, 3.0 or 3.5% larger outer diameter should be specified. For example, for a polypropylene tube having an inner diameter of 200 and / or 199.90 mm, the outer diameter (“OD”) of the flow distributor 24 is greater than 201.90 mm, for example 202-204, 202.5, 203, 203.5. , 204, 204.5, 205, 205.5 mm). The flow distributor 24 is designed with a specific nominal OD so as to induce sufficient hoop tension in the wall of the tube 20. In selecting an appropriate nominal OD, factors to consider are the physical properties of the constituent materials combined with a geometry that includes both the tolerance of the column tube ID and its wall thickness and the OD tolerance of the flow distributor 24. (E.g., friction coefficient, Young's modulus, elastic modulus, and yield point elongation). The force required to press-fit the assemblies together can be determined theoretically (for example by advanced analytical tools such as finite element analysis), and as an alternative, this rating is validated with specific components It may be done by ethical research.

Results Table 1 summarizes the data obtained from this series of experiments. At the time of pressurization, the internal pressure was measured while visually observing whether there was any leakage in the joining region from the tube to the end piece.

The press-fit liquid seal was linearly increased between 0.5 mm to 2.5 mm diameter allowance and the sealing capability improved by about 30 psi (~ 2 bar) with each additional millimeter. As the interference was increased from 2.5 mm to 3.5 mm, the sealing capacity increased by about 11 psi (˜0.76 bar). FIG. 14B is a plot of leakage pressure based on diameter tightening allowance and graphically illustrates the observed sealing tendency.

Table 1 further summarizes the data obtained when re-pressing a press-fit assembly that was fully welded (ie, the top and bottom end pieces were welded in place) to test the weld strength. Yes. The welded portion of the column tube with a 201 mm end piece yielded at 165 psi (11.4 bar). The welds of other assemblies were not testable until failure. No pressurization beyond the points reported in Table 1 was possible due to excessive leakage beyond the weld gap and / or thread entry / exit. Furthermore, in all columns except the test subject with an end cap diameter of 202 mm, the weld did not prevent the weld seam from leaking at / around the leak pressure observed prior to welding. FIG. 15 is a graphical representation of the observed weld strength of the four assemblies.

Results Table 2 , along with FIGS. 14a, 14b and 15, summarizes the data obtained from this series of experiments. At the time of pressurization, the internal pressure was measured while visually observing whether there was any leakage in the joining region from the tube to the end piece.

Table 2 further summarizes the data obtained when re-pressing a press-fit assembly that was fully welded (ie, both the upper and lower packs were welded to the tube wall) to test the weld strength. ing. The welded portion of the column tube with a 201 mm end piece yielded at 165 psi (11.4 bar). The welds of other assemblies were not testable until failure. No pressurization beyond the points reported in Table 2 was possible due to excessive leakage beyond the weld gap and / or thread entry / exit. Furthermore, in all columns except the test subject with an end cap diameter of 202 mm, the weld did not prevent the weld seam from leaking at / around the leak pressure observed prior to welding. FIG. 15 is a graphical representation of the observed weld strength of the four assemblies.

Claims (18)

A method for making and loading a chromatography column comprising:
Selecting a column tube having appropriate elasticity and an inner diameter and length to accommodate a desired volume of packing medium;
Selecting appropriately sized first and second flow distributors, wherein at least the second flow distributor has a diameter greater than the inner diameter of the tube, and the method further comprises:
Permanently securing the first flow distributor to the first end of the tube;
Loading a packing medium into the column tube;
An axial force is applied to insert the second flow distributor into the second end of the tube and push the second flow distributor into the column tube to establish an interference fit. Forming a sealed chamber between the first and second flow distributors;
(I) applying additional axial force to the second flow distributor until the second flow distributor reaches a desired location inside the column tube, or (ii) applying liquid to the chamber By pushing in and applying water pressure and returning the second flow distributor towards the second end of the tube or by any combination of (i) and (ii) Adjusting the longitudinal position of the second flow distributor;
Permanently securing the second flow distributor inside the tube when the second flow distributor is properly positioned.   The method of claim 1, wherein the column tube comprises plastic.   The method according to claim 1, wherein the second flow distributor is permanently fixed by welding.   4. A method according to any one of the preceding claims, wherein the diameter of the second flow distributor is about 0.25% to 5% greater than the inner diameter of the tube.   The method according to any one of claims 1 to 4, wherein no gap is formed between an outer peripheral surface of the second flow distributor and an inner surface of the tube as a result of the interference fit.   The first flow distributor has a diameter greater than the inner diameter of the tube, and the step of securing the first flow distributor to the first end of the tube applies an axial force to the first flow distributor. The method of claim 1, further comprising: inserting a first flow distributor into the first end of the tube to push the first flow distributor into the tube to establish an interference fit. Method.   7. The axial force for pushing the second flow distributor into the tube to establish the interference fit within the tube is between about 1000 lbf and about 10000 lbf. The method described.   The method according to any one of claims 1 to 7, wherein the inner surface of the tube includes a chamfer formed around at least one end of the tube.   9. A method according to any one of claims 1 to 8, wherein the first flow distributor is formed as an integral part of the tube.   10. A method according to any one of the preceding claims, wherein the packing medium comprises a slurry comprising about 40% to about 70% solids.   11. A method according to any one of the preceding claims, wherein the axial force establishes an induced hoop tension sufficient to create a hydrostatic seal. A method for making and loading a chromatography column comprising :
Selecting a column tube having an inner diameter and length to accommodate a particular volume of packing medium, and a particular elasticity and wall thickness;
Selecting a first and a second flow distributor, wherein at least the second flow distributor has an outer diameter greater than the inner diameter of the column tube, the method further comprising:
Permanently securing the first flow distributor to the first end of the column tube;
Loading a packing medium into the column tube;
Sufficient to apply an axial force to insert the second flow distributor into the second end of the column tube to provide an initial seal that prevents leakage of the packing medium without being permanently fixed. Pushing the second flow distributor into the column tube to a first longitudinal position with a tight interference fit;
Testing the performance of the loaded chromatography column;
(I) by applying an additional axial force to the second flow distributor, or (ii) pushing a liquid into the chamber to apply water pressure and connecting the second flow distributor to the second of the column tube. Optionally adjusting the initial longitudinal position of the second flow distributor within the column tube by returning toward the end of the column or by any combination of (i) and (ii) When,
Permanently securing the second flow distributor within the column tube at the final longitudinal position when the second flow distributor is moved to a final longitudinal position. . The method of claim 12, wherein the first longitudinal position of the second flow distributor is different from the final longitudinal position. The method of claim 12, wherein the first longitudinal position of the second flow distributor is the same as the final longitudinal position. The method of claim 12, further comprising testing the performance of the chromatography column after the second flow distributor is permanently secured within the column tube. 13. The method of claim 12, further comprising the step of retesting the performance of the chromatography column after adjusting the longitudinal position within the column tube of the second flow distributor. The method of claim 12, wherein the second flow distributor is permanently fixed when the performance of the chromatography column meets a specified performance level. 13. The method of claim 12, wherein the performance test of the chromatography column comprises (i) a theoretical plate equivalent height test, (ii) an asymmetry analysis test, or any combination of (i) and (ii). .